Literally dozens of animal studies indicate that offspring of prenatally stressed mothers exhibit a wide range of behavioral, physiological, and immunological impairments that persist into adulthood. Research into the mechanisms involved identifies the hypothalamic-pituitary-adrenal (HPA) axis as the most likely mediating mechanism, and further imply that this system may be "set" or "programmed" in utero. The relevance of these findings and of the programming mechanism to humans is unclear. There is now good correlational evidence that prenatal anxiety is associated with child outcomes, but translation from the animal model to humans is far from complete because of lingering questions about the causal nature of this link, the degree to which both behavioral and biological outcomes are affected, and the mechanisms involved. The proposed study will provide much-needed new information in this line of research by investigating causal hypotheses concerning the HPA axis, testing the links with behavioral and immune outcomes, and examining the role of early parent-infant relationship quality as a moderator of the effects of prenatal anxiety. 200 women, one-half of whom meet diagnostic criteria for anxiety, will be followed prospectively; data on psychological and physiological measures of anxiety will be collected on multiple occasions in pregnancy and the postnatal period. Obstetric, immune, cognitive, HPA axis, and behavioral/emotional outcomes in children will be collected at 2, 6, 12, and 16 months postnatally. For data on immune functioning, we will take advantage of naturally occurring immune stresses in the form of Hepatitis B and tetanus, and will document both B and T cell mediated responses. Scientifically, findings from the proposed multidisciplinary, prospective longitudinal study will provide essential data to evaluate the possibility that a "programming" mechanism associated with prenatal anxiety also exists in humans. These data will also carry substantial public health significance, particularly given what is known about the high prevalence of anxiety in pregnancy. Moreover, the detailed focus on immune function means that these observations will extend this research well beyond mental health, and may illuminate further the mechanisms by which early stress exposure influences psyche and soma. [unreadable] [unreadable] [unreadable]